Mammals have the remarkable ability to detect and discriminate thousands of odors. However, olfactory coding strategies in the olfactory sensory neurons are still largely unknown. Critical link between the odorant response spectra and the expressed receptors has just started to emerge and much less is known about how complex odor mixtures such as urine are encoded at the epithelial level. Our long-term goal is to address key issues in olfactory information coding and processing using the septal organ as a model. Functional studies on the main olfactory system have been hindered by its inherent complexity. In a mouse nasal cavity, there are approximately 3 million sensory neurons each of which expresses one out of about 1000 receptor genes and responds to a broad range of odorants. In contrast, the septal organ, an island of olfactory neuroepithelium located in the ventral base of the nasal septum, presents a much smaller system with approximately 14,000 neurons expressing about 40 receptor genes. The overall aim of the current proposal is to provide physiological, molecular and anatomical basis that defines the unique functions of this specialized organ. First, we will test the hypothesis that the septal organ is involved in sensing the urine odors because the septal glomerular area in the bulb is consistently activated by urine exposure. By combining optical imaging and patch clamp techniques, we will address the coding principles of complex odor mixtures, including interactions of the major urinary components at the single cell level. Second, we will identify the receptor genes in the septal organ using molecular cloning and Affymetrix genechip approaches. We will construct the expression maps of these receptor genes in both the septal organ and the main olfactory system, since most of these genes are shared by the two systems. We will also test the hypothesis that each neuron expresses only one receptor in the septal organ. Third, we will determine the primary targets in the olfactory bulb and subsequently in the olfactory cortex from the septal organ by neurotracing and gene-targeting techniques. The septal organ shares key features with the main olfactory epithelium, but with a manageable number of cells and receptor genes. Therefore, implementing such a project will greatly enhance our knowledge about olfactory coding in general and shed light on the behavioral significance of this enigmatic organ.